Coexistent frontal fibrosing alopecia with ophiasis pattern alopecia areata in a young female: A case report and review of the literature

Key Clinical Message This study highlights the possibility of coexistent Frontal Fibrosing Alopecia and ophiasis pattern Alopecia Areata especially in young females which is a rare manifestation. A concomitant shared pathophysiology is suspected to underlie this association.


| INTRODUCTION
Frontal fibrosing alopecia (FFA) is defined as band-like cicatricial alopecia on the frontotemporal area of the scalp.The condition can be associated with perifollicular inflammation and alopecia of other areas, including the eyebrow, axillae, pubic region, and extremities.The disorder is histopathologically characterized by lymphocytic infiltrate around the isthmus and infundibulum with a decrease in the number of follicles, which are replaced by fibrosis. 1lthough the exact underlying mechanism is not known, genetic and environmental factors are considered to be involved in FFA. 2 The disorder mainly affects postmenopausal women and rarely affects younger females, males, or children. 3A final diagnosis is confirmed through clinical examination and histopathological studies. 4][7] Alopecia areata (AA) is an autoimmune disease that destroys hair follicles.Ophiasis is a subtype of AA which manifests as a symmetric, band-like pattern of hair loss on the occipital, temporal, and parietal areas of the scalp.This subtype most commonly occurs above the ears on the lateral area of the scalp and is refractory to conventional treatment with corticosteroids, immunotherapy, and minoxidil. 8,9Studies have rarely reported coexistent FFA and AA in one case.In this paper, we report on a case of FFA associated with ophiasis.
the scalp and the forehead (Figures 1 and 2).The lesions were otherwise asymptomatic and had not increased in size during this period.She has experienced several episodes of exacerbation that were triggered by emotional stress and the wearing of a head band.The patient also complained of patches of hair loss on the scalp commencing at 4 years of age in a waxing and waning pattern.Past medical history was unremarkable for any specific disorder and she reported no associated signs and/or symptoms.She had not previously sought medical treatment for these problems.
Clinical examination indicated three patches of hair loss, two in the temporal area bilaterally (6 × 6 cm), and one in the occipital area (2 × 3 cm) which featured an ophiasis pattern of alopecia areata with exclamation point hairs at the periphery of the lesions.There was no erythema or erosion associated with the lesions.The frontal lesions were skin-colored papules that felt uneven in touch.Seborrheic dermatitis was an incidental finding during the examination with some erythema and dandruff on the scalp although the patient had not complained of this.

| METHODS
To confirm the diagnosis, a biopsy of the facial lesion was obtained, which was affirmative for frontal fibrosing alopecia.Histopathologic examination presented perifollicular lymphocytic infiltration, mainly around the isthmus and infundibulum portions, with basal layer vacuolar degeneration of the follicular epithelium.Villus hair follicles were also involved.A decrease in follicular density as well as a true fibrous band were observed (Figure 3).For treatment of the facial papules, isotretinoin (20 mg daily) and mometasone ointment were initiated to which the patient has responded well.

| CONCLUSION AND RESULTS
The ophiasis was treated with topical minoxidil and intralesional injection of triamcinolone acetonide and responded well to the treatment.At the follow-up visit after 8 weeks of treatment, complete symptom resolution was observed for all lesions.
Consistent with previous case reports, this paper highlights the possibility of FFA associated with AA at an especially young age.A concomitant shared pathophysiology is suspected to underlie this association and requires further investigation by researchers.

| DISCUSSION
1][12] To the best of our knowledge, this is the first case of ophiasis pattern AA associated with FFA in a premenopausal female to be reported.Although FFA mainly affects postmenopausal women, cases of younger females and males have been reported. 13nterestingly, our patient manifested the symptoms in the early years of life, which also has been rarely reported in the literature.A summary of the reported cases is presented in Table 1.
FFA and AA are diverse autoimmune variants of alopecia.Studies have suggested that the coexistence of both disorders is not incidental.Desai et al. 10 have reported seven cases of AA associated with FFA.In their study, four out of seven manifestations and diagnoses of AA preceded the development of FFA.In the other three cases, both disorders were diagnosed at the same time and the histopathological manifestations of FFA and AA were evident in one specimen.This suggests a foregoing pathophysiology of FFA, which may provoke further development of FFA.Similar results have been reported by Lin et al. 12 Consistent with earlier reports, our case developed ophiasis at 4 years of age and later developed FFA at 16 years of age.
Pathophysiologically, both disorders manifested with the loss of immune privilege of the hair follicles. 5FFA, as a variant of lymphocytic cicatricial alopecia, is characterized by irreversible scarring alopecia at the frontotemporal hairline and is associated with hair loss of the eyebrow and body. 14,15Pathological findings include lymphocytic inflammatory infiltrate surrounding the bulge of the hair follicle and perifollicular concentric fibrosis, causing follicular damage and fibrosis. 14A manifests with alopecic patches on the scalp. 14he main histopathological findings are lymphocytic infiltrate around the bulb of the hair follicles, an increasing number of telogen follicles and miniaturization of hair follicles. 14he hair follicle is considered as an immune privilege site.Because it is able to evade the immune system by downregulation of major histocompatibility complex proteins, increasing the production of local immunosuppressants and impaired antigen-presenting cells act as an extracellular matrix barrier that inhibits disruption by immune cells.This immune privilege site was considered to be limited to the anagen bulb; however, recent studies have shown that it also affects the bulge, which protects the stem cells. 14As mentioned earlier, the site of the inflammatory infiltrate is a major difference between AA and FFA, which affect the bulb and bulge, respectively. 16herefore, the loss of stem cells and epithelial mesenchymal transition in the bulge of follicles that have been affected by FFA can result in further scarring. 16However, it is as yet unclear whether or not an underlying disorder triggers the immune system to target hair follicles simultaneously in these two conditions or if they are caused by disorders of the immune system that manifest at the same time.Further research is highly encouraged in this regard.
A diagnosis can be made based on clinical findings along with histopathological studies for both conditions.Treatment commonly includes intralesional and topical steroids, minoxidil, excimer laser, finasteride, and hydroxychloroquine for FFA and corticosteroids, minoxidil, anthralin, and immunosuppressants for AA. 14,17Our case responded well to treatment with isotretinoin with topical corticosteroid for FFA and minoxidil with intralesional corticosteroids for ophiasis.Although ophiasis is usually refractory to treatment, complete symptom resolution for all lesions was observed after 8 months in our case.

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I G U R E 1 Skin-colored papules at the front of the scalp and forehead.F I G U R E 2 Patches of hair loss on the scalp.